Pain is one of the basic clinical symptoms seen by every physician and is usually categorized into three segments: mild, moderate and severe. The mild-to-moderate segment has multiple product entries including aspirin, acetaminophen, ibuprofen, and other non-steroidal, anti-inflammatory (NSAID) products. Narcotic analgesics remain the mainstay of currently marketed products for the treatment of moderate-to-severe pain.
Cancer and the post-operative surgical period are two conditions most often associated with moderate-to-severe pain. Tumor infiltration of bone, nerve, soft tissue or viscera are the most common causes of cancer pain accounting for 65-75% of patients. Pain as a result of cancer treatment from surgery, chemotherapy or radiation accounts for 15-25% of patients, with the remaining 5 -10% reporting pain independent of their cancer or cancer therapy. Various factors influence the prevalence of cancer pain including the primary tumor type, stage and site of disease and patient variables, especially psychological variables. Similarly, patient response to post surgical pain is dependent upon location and extent of intervention as well as personal attributes. However, post surgical pain is distinguished from cancer pain by length of treatment period.
The major concern with narcotics, which constitute the largest segment of the U.S. market for treatment of moderate-to-severe pain, is the potential for addiction and loss of activity (i.e. tolerance) with continued use. Consequently, there is a need for other analgesics that can relieve pain, especially moderate-to-severe pain associated with cancer. In order to improve analgesic responsiveness and reduce side effects, research efforts have focused on both drug delivery strategies and novel drug entities. Newer drug delivery strategies include transdermal narcotics, PCA, intraspinal implantation of controlled release pumps and implantation of encapsulated living cells which release naturally-occurring endorphins or other analgesic peptides. New drug approaches reflect the varying pathways and causes of moderate-to severe pain. Classes of compounds in development for treating pain include serotonergics, noradrenergics, opioid partial agonists and kappa opioid agonists. Therapeutic targets with significant preclinical investigation include tachykinin/bradykinin antagonists and excitatory amino acid antagonists. Newer targets being exploited include growth factors, cytokines, nitride oxide regulators, etc. Natural sources including folk medicine remedies and frog venom extracts are also under investigation.
Investigations of spider venoms for identification of biological entities with commercial potential has focused primarily on the agrochemical sector. The ultimate goal of these activities has been the search for chemical constituents which interact selectively with invertebrate species to induce paralysis and/or death with minimal mammalian toxicological properties. However, in recent years, spider venoms have joined other predator-derived venoms being exploited for identification of compounds which identify mammalian targets and which assist the development of pharmaceuticals. The arachnid species Grammostola spatulata, commonly referred to as the Chilean pink tarantula spider, is a member of the Theraphosidae family and the Chelicerata order. Previous studies by Lampe et al. (1993) Molecular Pharmacology 4:451-460 showed that venom of Grammostola spatulata contains a peptide which interacts in a non-selective manner with voltage-sensitive calcium channels.